Cells cultured on flat cell culture ware often provide artificial two-dimensional sheets of cells that may have significantly different morphology and function from their in vivo counterparts. Cultured cells are important to modern drug discovery and development and are widely used for drug testing. However, if results from such testing are not indicative of responses from cells in vivo, the relevance of the results may be diminished. Cells in the human body experience three dimensional environments completely surrounded by other cells, membranes, fibrous layers, adhesion proteins, etc. Thus, cell culture apparatuses that better mimic in vivo conditions and that prompt cultured cells to have in vivo-like morphology and function are desirable.
Much progress has been made in cell culture configuration and systems to better mimic in vivo conditions and maintain differentiated cells, such as hepatocytes, in culture for longer periods of time. For example, collagen sandwich culture systems, 3D cell culture, and microfluidic perfusion systems have provided some enhancement in cell performance relative to conventional cultures devices in maintaining viable cell cultures with some phenotypic relevance. Other methodologies that have been used to prolong cell viability and function include the use of modified cell culture media, co-cultures, and the use of various extracellular matrices to promote 3D cellular organization. However, mimicking complex in vivo microenvironment that modulates cellular function for successful long-term cultures of cells remains a challenge. Accordingly, even with such advances, limited improvement in cell cultured cell function has been achieved.